What is the best means to diagnose Helicobacter (H) Pylori infection?

Best Means to Diagnose H. Pylori Infection

For initial diagnosis of H. pylori infection, the urea breath test (UBT) is the most accurate non-invasive test with sensitivity of 94-97% and specificity of 95%, making it the preferred first-line diagnostic method in clinical practice. 1

Primary Non-Invasive Tests (First-Line)

The American College of Gastroenterology and European guidelines recommend two primary non-invasive tests for diagnosing active H. pylori infection: 1

Urea Breath Test (UBT) - First Choice

• UBT is the gold standard non-invasive test, detecting active infection by measuring urease activity with sensitivity of 94-97% and specificity of 95%. 1
• The test requires patients to fast for at least 6 hours before testing for optimal accuracy. 1
• UBT is safe in all populations, including children and pregnant women (using 13C-UBT, not radioactive 14C). 2
• This test detects only active infection, not past exposure, making it valuable for both initial diagnosis and post-treatment confirmation. 2

Stool Antigen Test - Excellent Alternative

• Laboratory-based validated monoclonal stool antigen test is equally accurate with sensitivity and specificity of approximately 93%, comparable to UBT. 1, 2
• This test directly detects H. pylori bacterial antigens in stool specimens and confirms active infection only. 1, 3
• Critical caveat: Only laboratory-based monoclonal antibody tests achieve high accuracy—rapid in-office immunochromatographic tests have significantly lower accuracy (80-81%) and should be avoided. 1, 2
• The stool antigen test is more cost-effective than UBT while maintaining comparable accuracy. 2

Tests to Avoid for Initial Diagnosis

Serology - Not Recommended

• Serological tests should NOT be used for routine diagnosis because they cannot distinguish between active infection and past exposure, with overall accuracy averaging only 78% (range 68-82%). 1, 2
• Antibody levels persist in blood for months to years after eradication, leading to false-positive results. 1, 2
• Never use serology to confirm eradication after treatment. 1, 2
• The only limited exception: validated IgG serology may be considered when patients have recently used PPIs or antibiotics and medication washout is not possible. 1

Invasive Tests (When Endoscopy is Performed)

When endoscopy is clinically indicated, the following tests can be performed on biopsy specimens: 1

Histological Examination

• Histology is the gold standard among invasive tests, particularly when using immunohistochemistry, which has high sensitivity and specificity. 1
• Requires at least two biopsy samples from both the antrum and body for improved sensitivity. 1
• Allows visualization of bacteria and assessment of mucosal damage. 2

Rapid Urease Test (RUT)

• Pre-treatment sensitivity ranges from 80-95% with specificity of 95-100%. 1
• Requires approximately 10^4 organisms for a positive result. 1
• Provides quick results during endoscopy. 2

Culture

• Provides definitive proof of infection and allows antimicrobial susceptibility testing. 1
• Particularly valuable after treatment failure when antimicrobial resistance is suspected. 1, 2
• Technically demanding with variable sensitivity between laboratories. 1

Critical Medication Washout Requirements

False-negative results occur with all tests (except serology) if proper medication washout is not followed: 1, 2

• Proton pump inhibitors (PPIs): Stop at least 2 weeks before testing 1, 2
• Antibiotics: Stop at least 4 weeks before testing 1, 2
• Bismuth compounds: Stop at least 4 weeks before testing 1
• Histamine-2 receptor antagonists do not affect bacterial load and can be substituted for PPIs when acid suppression is needed before testing. 2

Algorithm for Test Selection

For Primary Care Setting (Young Patients <50 Years Without Alarm Symptoms)

1. First choice: 13C-urea breath test OR laboratory-based monoclonal stool antigen test 1, 2
2. If patient recently used antibiotics or PPIs and cannot wait for washout period, consider validated IgG serology as temporary alternative. 1, 2

For Patients Requiring Endoscopy

Endoscopy is indicated for: 2

• Patients with alarm symptoms (bleeding, weight loss, dysphagia, palpable mass)
• Older patients (≥50 years) with new-onset dyspepsia
• Patients who failed eradication therapy needing culture and antimicrobial sensitivity testing

During endoscopy, perform: rapid urease test, histology, or culture. 2

Confirmation of Eradication

• Testing should be performed no earlier than 4 weeks after completion of treatment. 1, 2
• Use UBT or laboratory-based monoclonal stool antigen test—never use serology. 1, 2
• Ensure proper medication washout before confirmation testing. 1, 2

Common Pitfalls to Avoid

• Using rapid in-office serological or stool tests instead of laboratory-based validated tests. 1, 2
• Testing too soon after treatment completion (must wait at least 4 weeks). 1, 2
• Failing to stop PPIs before testing, leading to false-negative results in all tests except serology. 1, 2
• Using serology to confirm eradication—antibodies remain elevated after elimination. 1, 2
• Using panels of IgG, IgA, and IgM tests, which provide no added benefit over validated IgG tests. 2